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(Reference retrieved automatically from Web of Science through information on FAPESP grant and its corresponding number as mentioned in the publication by the authors.)

Topological robustness analysis of protein interaction networks reveals key targets for overcoming chemotherapy resistance in glioma

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Author(s):
Azevedo, Hatylas [1] ; Moreira-Filho, Carlos Alberto [1]
Total Authors: 2
Affiliation:
[1] Univ Sao Paulo, Fac Med, Dept Pediat, Sao Paulo, SP - Brazil
Total Affiliations: 1
Document type: Journal article
Source: SCIENTIFIC REPORTS; v. 5, NOV 19 2015.
Web of Science Citations: 19
Abstract

Biological networks display high robustness against random failures but are vulnerable to targeted attacks on central nodes. Thus, network topology analysis represents a powerful tool for investigating network susceptibility against targeted node removal. Here, we built protein interaction networks associated with chemoresistance to temozolomide, an alkylating agent used in glioma therapy, and analyzed their modular structure and robustness against intentional attack. These networks showed functional modules related to DNA repair, immunity, apoptosis, cell stress, proliferation and migration. Subsequently, network vulnerability was assessed by means of centrality-based attacks based on the removal of node fractions in descending orders of degree, betweenness, or the product of degree and betweenness. This analysis revealed that removing nodes with high degree and high betweenness was more effective in altering networks' robustness parameters, suggesting that their corresponding proteins may be particularly relevant to target temozolomide resistance. In silico data was used for validation and confirmed that central nodes are more relevant for altering proliferation rates in temozolomide-resistant glioma cell lines and for predicting survival in glioma patients. Altogether, these results demonstrate how the analysis of network vulnerability to topological attack facilitates target prioritization for overcoming cancer chemoresistance. (AU)

FAPESP's process: 11/50761-2 - Models and methods of e-Science for life and agricultural sciences
Grantee:Roberto Marcondes Cesar Junior
Support Opportunities: Research Projects - Thematic Grants